The anesthetic bupivacaine induces cardiotoxicity by targeting L-type voltage-dependent calcium channels

OBJECTIVE: Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully elucidated, thus we aimed to examine this mechanism. METHODS: We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca(2+)) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest. RESULTS: In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca(2+) currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of Ca(V)1.3 (L-type) Ca(2+) channels, which may be regulated by the multifunctional protein calreticulin. CONCLUSIONS: The present study identifies a possible role of the calreticulin–Ca(V)1.3 axis in bupivacaine-induced abnormal action potentials and Ca(2+) currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.